My proposed studies include the following: (1) The isometice twitch contraction time of skeletal muscle is generally believed to be regulated by the activity of myosin ATPase. However, I have found evidence that the rate of sarotubular Ca ions uptake is the primary factor determining the contrction time. Isometric contraction times are known to undergo changes in developing rat muscles and in denervated cat and rabbit muscles. To determine which factor is more closely related to contraction time, I plan to measure myosin ATPase and sarcotubular Ca ions uptake activities in these muscles. (2) I have found an increase in the specific activity of K ion-independent p-nitrophenylophosphatase in sarcolemma isolated from denervated rat hind-limb muscles. I plan to assay this enzyme in muscle biopsy specimens from patients with denervating diseases, such as amyotrophic lateral sclerosis and diabetic neuropathy, in order to see if the activity of this enzyme can be used as a diagnostic indicator of denervation in man.